Monoclonal antibodies directed against the model protein antigen, lysozyme, c, are used as probes to study antibody-protein interactions and structure-function relationships and to study developmentally regulated antigens in normal and neoplastic development. The interaction of antibodies with the epitopes are modelled and ultimately refined by protein crystallography studies. One antibody has been studied in detail; the computer refined combining site is a shallow concavity bordered by hydrophobic segments. The computer fitted complex of this antibody with the proposed epitope in lysozyme indicates a very extensive contact interface involving antibody framework residues as well as 5 out of 6 complementarity determining regions. The opposing surfaces of the antibody and antigen are highly complementary in shape, charge, and hydrophobic properties, and side chain-to-backbone hydrogen bonds predominate in the interaction between antibody and antigen. Chain recombination experiments have allowed further definition of likely contact residues with HEL and have in addition provided evidence for a hierarchy of structure-function determination. Experiments to test hypothesized structure-function correlates utilizing site specific mutagenesis of in vitro expressed immunoglobulin genes are in progress. Monoclonal antibodies are being generated against bacterially expressed mouse c-myc protein; these antibodies will be used to purify and characterize structure-function relationships in the myc protein, applying the principles derived from the model protein studies.